Abstract 5223: IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma

Abstract

Abstract Purpose: Chronic hepatic inflammatory cytokine interleukin 6 (IL-6) appears important role in pluripotent transcription factor OCT4 expression particularly in HBV-related hepatocellular carcinomas (HBV-HCC). However, the underlying mechanism still remains largely unknown. Experimental Design: Serum levels of IL-6 were detected using ELISA assays (n = 120). The effects of IL-6 on DNMT/OCT4 expression in HCC were examined using real-time QPCR analysis, RNA interference, and xenograft animal models. The DMNT/OCT4 protein and phospho-STAT (p-STAT) were detected by western blotting. OCT4, and DNMT expression levels in tissues (n = 144) were analyzed by real-time Q-PCR and was correlated with early tumor recurrence using Kaplan-Meier survival analysis. Results: A high positive correlation between the expression levels of OCT4 and epigenetic DNMT family in human HCC tissues was observed. High serum levels of IL-6 were significantly correlated with high OCT4 and DNMT expression. IL-6 stimulated the DNMT expression STAT3-dependently, which stimulated the OCT4 expression in both the cell lines and the xenografted mouse tumors. The inhibition STAT phosphorylation/DNMT expression by dominant negative STAT-Y705F plasmid transfection or DNMT RNA interference significantly suppressed the IL-6-induced OCT4 expression in vitro. Conclusions: The expression of pluripotency-related OCT4 is associated with early tumor recurrence and is regulated by IL-6-induced epigenetic DNMTs in HCC. Citation Format: Ssu-Chuan Lai, Te-Sheng Chang, Yu-Ting Su, Yu-Chih Wu, Yung-Che Kuo, Pei-Chi Lan, Yen-Hua Huang. IL-6 regulates the OCT4 expression by epigenetic modulation in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5223.